Phosphonium, triphenyl(3,7,11-trimethyl-2,4,6,10-dodecatetraenyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

March 22, 1996

GLP compliance:

yes

Remarks:

Study director

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

triphenyl[(2E,4E,6E)-3,7,11-trimethyldodeca-2,4,6,10-tetraen-1-yl]-λ⁵-phosphane

EC Number:

603-493-6

Cas Number:

131560-11-7

Molecular formula:

C33 H38 P

IUPAC Name:

triphenyl[(2E,4E,6E)-3,7,11-trimethyldodeca-2,4,6,10-tetraen-1-yl]-λ⁵-phosphane

Test material form:

semi-solid (amorphous): gel

Details on test material:

Charge: B 15S
Purity: 78.7 g/100 g (HPLC)
State: highly viscous gel

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Manufacturing date: August 1998

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, exclusion of oxygen (under nitrogen)
- Solubility and stability of the test substance in the solvent: proven good solubility

FORM AS APPLIED IN THE TEST: solution

Test animals

Species:

rat

Strain:

Wistar

Remarks:

chbb: thorn

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: young
- Weight at study initiation: 177-180 g (male), 175-181 g (female)
- Fasting period before study: animals were given no feed at least 16 hours before administration, but water was available ad libitum
- Housing: single in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

bidest

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

200 mg/kg (2 kg/ 100 mL), 2000 mg/kg (20 kg/ 100 mL) only tested in three separate females

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days for the 200 mg/kg dose group; 1 day for the 2000 mg/kg dose group
- Frequency of weighing: shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period)
- Clinical signs including body weight recorded several times on the day of administration
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - <= 2 000 mg/kg bw

Mortality:

2000 mg/kg dose group: all animals died 1 day after application
200 mg/kg dose group: delayed mortality observed in 1 male and 1 female rat, which died 6 and 11 days after application, respectively

Clinical signs:

other: 2000 mg/kg dose group: impaired general state and dyspnoea 200 mg/kg dose group: impaired and poor general state, dyspnoea, gasping, apathy, staggering, spastic gait, diarrhea, exsiccosis, extended abdomen, red discoloured urine, compulsary gnawing and re

Gross pathology:

- dilation of the stomach and of the small and large intestine with gaseous or watery contents and erythema of the small intestine

Any other information on results incl. tables

Table 1: Symptoms of the male animals (cageside observations)

Dose (mg/kg) 200	numer animals (n) with symptoms	time period showing symptoms
Impaired general state	3/3	h1 d1-d2
Poor general state	3/3	d1-d2
Dyspnoea	3/3	h1-h4 d5-d9
Gasping	1/3	h1-d2
Apathy	3/3	h1-h4
Staggering	1/3	h1-h4
Piloerection	3/3	h1-d9
Diarrhea	1/3	h3-h4
Exsiccosis	1/3	d5-d9
Weight reduction	1/3	d7-d9
Extended abdomen	1/3	d9
Red clammy snout	1/3	d1

h: hour, d: day

Table 2: Symptoms of the female animals (cageside observations)

Dose (mg/kg)	200		2000
	numer animals (n) with symptoms	time period showing symptoms	numer animals (n) with symptoms	time period showing symptoms
Impaired general state	1/3	d6-d9	3/3	h2-h4
Poor general state	3/3	h1-h5 d2-d3
Dyspnoea	3/3	d2-d3 d2-d9	3/3	h2-h4
Apathy	3/3	h1-h5 d2-d3
Staggering	3/3	h5 d2-d3
Spastic gait	1/3	d3
Piloerection	3/3	h5 d2-d9
Smeared fur	2/3	d2-d3
Diarrhea	3/3	h5
Exsiccosis	2/3	d2-d3
Discoloured urine red	1/3	d3
compulsory gnawing	3/3	h1-h2
Red clammy snout	2/3	d2-d3

h: hour, d: day

Table 3: Mortality of the female animais (cumulative)

Dose	(mg/kg):	200
No.of	animals:	3
after:
h0		0
d11		1
d14		1

Table 4: Mortality of the female animais (cumulative)

Dose	(mg/kg):	200	2000
No.of	animals:	3	3
after:
d1		0	3
d6		1
d14		1

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 200 mg/kg and less or equal to 2000 mg/kg body weight.